【作者】 周美锋；

【导师】 何其庄；

【作者基本信息】 上海师范大学 ， 应用化学， 2008， 硕士

【摘要】 近年来金属配合物在抗菌、抗肿瘤以及与DNA相互作用等方面的研究一直是生物无机化学研究的热点。本文则以稀土离子和铜离子在这三方面的生物性能为着眼点,合成了10种纳米稀土谷氨酸咪唑三元配合物（简称纳米稀土配合物）和8种稀土-铜甘氨酸咪唑异核金属配合物（简称稀土-铜配合物）。通过元素分析、摩尔电导、红外光谱、紫外光谱、氢谱、碳谱、XRD、差热-热重以及TEM等方法对它们的组成、结构和形貌进行了表征,确定了它们的化学组成为:RE（Glu）₃ImCl₃·3H₂O(RE³⁺=La³⁺,Ce³⁺,Pr³⁺,Nd³⁺,Sm³⁺,Er³⁺,Eu³⁺,Y³⁺,Gd³⁺,Dy³⁺; L-Glu =C₅H₉NO₄;Im=C₃H₄N₂)和RECu₆（μ-OH）₃（Gly）₆Im₆Cl₆(RE³⁺=La³⁺,Ce³⁺,Pr³⁺,Nd³⁺, Sm³⁺, Er³⁺,Eu³⁺,Y³⁺;L-Gly=C₂H₅NO₂;Im=C3H₄N₂)。采用培养基扩散法和营养肉汤稀释法测定了上述18种金属配合物的抗菌活性,结果表明:所合成的这18种金属配合物对大肠杆菌、金黄色葡萄球菌和白色念珠菌均具有较好的抗菌性,属于广谱抗菌剂,且具有耐久性和长效性。采用形态学观察、MTT比色实验和流式细胞仪检测等方法研究了纳米稀土镧配合物、镧-铜配合物对K562白血病肿瘤细胞的凋亡和生长的抑制作用。结果表明:该两种金属配合物均能够诱导K562肿瘤细胞凋亡,抑制其生长,但是有浓度依赖性和时间依赖性;并且它们对K562肿瘤细胞的凋亡率和生长抑制率均高于其相应配体。采用紫外吸收光谱、荧光光谱、粘度分析和琼脂糖凝胶电泳分析等方法研究了纳米稀土镧配合物和镧-铜配合物与DNA的相互作用模式。结果表明:该两种金属配合物都是以部分插入模式与DNA相互作用的,其中镧-铜配合物对DNA的插入模式稍强一些,测得其与DNA的结合常数约为3.78×10⁴ L·mol^-1,而且该配合物还能够有效切割pBR322DNA,但是有浓度依赖性。更多还原

【Abstract】 In recent years, the development of metal complexes have been the active field of bioinorganic chemistry in the study of antibacterial, antitumor and with DNA interaction. On the biological properties of RE³⁺ and Cu2+, ten new nano-rare earth complexes with L-glutamic acid and imidazole,and eight rare earth-copper complexes with L-glycine and imidazole were synthesized.Their composition and structure was characterized by elemental analysis,molar conductance, IR, UV, 1HNMR, 13CNMR, X-RD, TG-DTA and TEM etc.The compositions of the complexes were confirmed to be RE（Glu）₃ImCl₃·3H₂O(RE³⁺=La³⁺,Ce³⁺,Pr³⁺,Nd³⁺,Sm³⁺,Er³⁺, Eu³⁺,Y³⁺,Gd³⁺,Dy³⁺; L-Glu =C₅Hv9NO₄; Im=C₃H₄N₂)and RECu₆（μ-OH）₃（Gly）₆Im₆Cl₆(RE³⁺=La³⁺,Ce³⁺,Pr³⁺,Nd³⁺, Sm³⁺,Er³⁺,Eu³⁺,Y³⁺; L-Gly=C₂H₅NO₂; Im= C₃H₄N₂)。The antibacterial activities of the complexes were evaluated by the agar diffusion method and nutrition broth dilution method. The results indicated that all the eighteen complexes exhibited excellent antibacterial activities against Escherichia coli, Staphylococcus aureus and Candida albicans,their antimicrobial spectrum were broad and have durable quality.The antitumor activity of the nano-rare earth La complex and La-Cu complex in vitro were researched by morphological observation, MTT assay and Flow Cytometry. The results showed that the two complexes all could induced K562 tumor cells apoptosis and inhibited their growth,but the cell apoptosis rate and the inhibition rate both higher than their ligands and have concentration-dependent and time-dependent.The interaction of the nano-rare earth La complex and La-Cu complex with DNA were studyed by UV, fluorescence spectrum, viscosity analysis and agarose gel electrophoresis etc.The results indicated that the interaction of the two complexes would bind DNA mainly by partially intercalation and the La-Cu complex could cleave pBR322DNA effectively,but has concentration-dependent.更多还原